Research Summary

Dysfunction of brain dopamine neurons is critically involved in the pathology of several neurologic and psychiatric disorders. Dr Elsworth’s research focuses on the “development, dysfunction, and demise” of dopamine neurons. The goal is to understand the mechanisms underlying the particular susceptibility of dopamine neurons to damage, and devising strategies for protecting, repairing or replacing these cells.

Dysfunction of brain dopamine neurons is critically involved in the pathology of several neurologic and psychiatric disorders. Dr Elsworth’s research focuses on the “development, dysfunction, and demise” of dopamine neurons. The goal is to understand the mechanisms underlying the particular susceptibility of dopamine neurons to damage, and devising strategies for protecting, repairing or replacing these cells.

Extensive Research Description

Dysfunction of dopamine neurons is implicated in several psychiatric or neurological disorders, notably Parkinson’s disease and schizophrenia. During the prenatal period the fetal brain undergoes dramatic changes, as structures and connections form according to strict spatial and temporal criteria. It follows then that during development environmental insults have greater potential to exert profound and permanent changes than other times during life and may affect the risk of the offspring succumbing to CNS disorders. A major focus of investigations is our finding of varying susceptibility of primate dopamine neurons to damage at different periods of development. Our research has identified prenatal phases when primate DA neurons are especially vulnerable to oxidative stress or endocrine disruptors and other times during development when they are remarkably resistant to such damage. These models offer insight into biochemical factors that may contribute to dopamine-dependent disorders later in life, and also provide novel strategies and mechanisms for protecting and preserving adult dopamine neurons.

Another field of research is investigation of the regulation of dopamine neurons innervating the prefrontal cortex, as our research has indicated that this input appears to regulate changes in dendrites and synapses, which are critical to the executive functions of this brain region. Experimental restoration of normal dopamine transmission in the prefrontal cortex would enable treatment of cognitive deficits that are characteristic of Parkinson’s disease and schizophrenia.

Other research is focused on repair of the damaged nigrostriatal dopamine system, using strategies such as implants of modified stem cells and neurotrophic factor gene therapy, with direct relevance to the treatment of Parkinson’s disease.